Premixes comprising active principles are currently used for orally delivering active compounds to animals, in particular to farm animals. These premixes are generally composed of a premix carrier of mineral or vegetal origin, a small quantity of active principles, and additives and excipients. They are easily incorporated to food, according to specific instructions of dosage, which allow the oral deliverance of the right dose of the active principle to the animals.
Drawbacks of this method are mainly the lack of homogeneity when the premix is incorporated into the animal food. Indeed, even if the blending is performed carefully, obtaining a homogeneous mix is challenging, due to the huge differences between the premix and the food ingredients, in terms of particles size, weight, hydrophilic and lipophilic features. Moreover, many active principles have electrostatic characteristics that make it difficult to homogenize the blend, since these compounds tend to accumulate in dead areas, on the walls of the blenders and of food containers.
These drawbacks are of particular relevance when the active components of the premix are beta agonists. Beta agonists are used to increase the rate of weight gain, to improve feed efficiency and increase carcass leanness during the last days on feed of breeding animals. Among them, the compound zilpaterol hydrochloride is widely used under the form of a premix, sold under its trade name ZILMAX® (animal feed containing zilpaterol hydrochloride). Zilpaterol is typically fed in the last three-six weeks of cattle's lives, with a brief period before death for withdrawal, which allows the drug to leave the animal's tissues. Process for its preparation is described in U.S. Pat. No. 5,731,028.
For these pharmaceutical ingredients, the recommended dose is about 5 to 20 grams per ton of animal food, and these extreme levels are very challenging in terms of homogeneity of the final mix. The lack of homogeneity in the animal food can induce a variation of consumptions of the active principles. If the proper dose is not administered in an uniform way in all animals, there will be a lack of uniformity in the benefits expected by the farmer.
Various strategies have been developed for obtaining more homogeneous premix and final mix.
U.S. Pat. No. 5,624,710 describes a premix wherein the granules supporting the active substances are coated with a water-soluble substance. It also describes the process for preparing said granular premix with particles having a diameter about the same size than the particles of animal feed, ranging between about 100 and 1,000 microns (μm).
The patent application EP 197 188 suggests the use of a non-ionic, physiologically compatible surfactant, to be sprayed during the blending of the premix, in order to limit the dust formation during the blending. These surfactants are for example monoesters of propylene glycol and of alimentary fatty acids. Moreover, this premix is characterized with a specific particle size of the support, between 300 and 800 microns, and a specific particle size of the active ingredient, between 50 to 200 microns.
The commercialized product ZILMAX® is produced by a process wherein the zilpaterol is dissolved in a fluid and sprayed onto the premix carrier (i.e. corn particles). The mixture is then dried and sieved. This long, expensive and environmental unfriendly process does not enable a suitable homogeneity of the mixture. Indeed, when this premix is blended with the animal feed, a variation coefficient staying above 10% in the final mix is observed, which is unacceptable.
On the contrary, in the present invention, zilpaterol is not dissolved in a fluid but is mixed in solid form with the premix carrier. The particle size of the premix carrier, and of the zilpaterol, are described hereunder. The present invention provides a very good homogeneity of the final mixture while being easier, faster and cheaper to put into practice.